ArticlePLoS pathogens2017
Streptococcus pneumoniae in the heart subvert the host response through biofilm-mediated resident macrophage killing.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
54 citing papers in PubMed, 71 citations in OpenAlex.
- Article
- Determinants of susceptibility and tolerance ofInfection and immunity · 2026Review
- Future Pneumococcal Vaccines: Shifting from Capsular Polysaccharides to Protein-Based Immunogens.Vaccines · 2026Review
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- Allele-specific zinc metalloprotease B influences cardiac damage during invasive pneumococcal disease.Cell reports · 2025Article
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- Heme-mediated selection of encapsulatedEmerging microbes & infections · 2025Article
- Pneumococcal HbioRxiv : the preprint server for biology · 2025Article
- Label-free microscopy enables high-throughput identification of genes controlling biofilm development.bioRxiv : the preprint server for biology · 2025Article
- Dual RNA isolation from blood: an optimized protocol for host and bacterial RNA purification for dual RNA-sequencing analysis in whole blood sepsis samples.Microbial genomics · 2025Article
- Pneumococcal Myocarditis in an Immunocompetent Young Adult: A Case Report and Literature Review.Cureus · 2025Article
- Structure, Function, and Regulation of LytA: TheMicroorganisms · 2025Review
- Pneumococcal Endocarditis: Historical Insights and Modern Challenges.Journal of community hospital internal medicine perspectives · 2025Article
- Infectious factors in myocarditis: a comprehensive review of common and rare pathogens.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2024Review
- Article
- The inflammatory spectrum of cardiomyopathies.Frontiers in cardiovascular medicine · 2024Review
- The Global Burden of Community-Acquired Pneumonia in Adults, Encompassing Invasive Pneumococcal Disease and the Prevalence of Its Associated Cardiovascular Events, with a Focus on Pneumolysin and Macrolide Antibiotics in Pathogenesis and Therapy.International journal of molecular sciences · 2023Review
- Acute organ injury and long-term sequelae of severe pneumococcal infections.Pneumonia (Nathan Qld.) · 2023Review
- Establishment of Streptococcus suis Biofilm Infection ModelMicrobiology spectrum · 2023Article
- The Two-Component System YesMN Promotes Pneumococcal Host-to-Host Transmission and Regulates Genes Involved in Zinc Homeostasis.Infection and immunity · 2023Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
For over 130 years, invasive pneumococcal disease has been associated with the presence of extracellular planktonic pneumococci, i.e. diplococci or short chains in affected tissues. Herein, we show that Streptococcus pneumoniae that invade the myocardium instead replicate within cellular vesicles and transition into non-purulent biofilms. Pneumococci within mature cardiac microlesions exhibited salient biofilm features including intrinsic resistance to antibiotic killing and the presence of an extracellular matrix. Dual RNA-seq and subsequent principal component analyses of heart- and blood-isolated pneumococci confirmed the biofilm phenotype in vivo and revealed stark anatomical site-specific differences in virulence gene expression; the latter having major implications on future vaccine antigen selection. Our RNA-seq approach also identified three genomic islands as exclusively expressed in vivo. Deletion of one such island, Region of Diversity 12, resulted in a biofilm-deficient and highly inflammogenic phenotype within the heart; indicating a possible link between the biofilm phenotype and a dampened host-response. We subsequently determined that biofilm pneumococci released greater amounts of the toxin pneumolysin than did planktonic or RD12 deficient pneumococci. This allowed heart-invaded wildtype pneumococci to kill resident cardiac macrophages and subsequently subvert cytokine/chemokine production and neutrophil infiltration into the myocardium. This is the first report for pneumococcal biofilm formation in an invasive disease setting. We show that biofilm pneumococci actively suppress the host response through pneumolysin-mediated immune cell killing. As such, our findings contradict the emerging notion that biofilm pneumococci are passively immunoquiescent.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.